Characterization of Methylation Pattern in Human Germ Cells of Patients Undergoing ICSI Treatment
Study Details
Study Description
Brief Summary
There is increasing evidence that exposure to environmental factors in early development is associated with an increased risk of metabolic and other common diseases. These increased disease risks are likely due to environmental-induced epigenetic changes leading to dysregulation of genes and signaling cascades. The best studied epigenetic modification in this context is DNA methylation. Preliminary studies have already shown that an increased father age or intracytoplasmic sperm injection affects methylation pattern in sperm or umbilical cord blood of children. Unlike sperm, less is known about the methylation of human oocytes and their susceptibility to environmental factors. The aim of this study is to analyze the methylation pattern of immature oocytes of women with decreased fertility. Based on the results of a large number of oocytes from different women, risk assessments could be made for individual factors such as the age of the patient, as well as correlations between the occurrence of changes in gene expression and the unfulfilled desire to have children. In addition, the methylation patterns in sperm from 20 patients are to be examined as reference patterns.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Although more than five million children have been conceived worldwide through Assisted Reproduction Techniques (ARTs), little is known about potential effects of ART in later life. So far, the focus of reproductive research is based on the success rate of infertility treatment. There is increasing evidence that exposure to environmental substances, age of the patient or in vitro culture conditions in early development is associated with a life-long increased risk of metabolic and other common diseases. These increased disease risks are likely due to environmental-induced epigenetic changes leading to dysregulation of genes and signaling cascades. These include Beckwith-Wiedemann and Angelman syndrome.
The best studied epigenetic modification in this context is DNA methylation, which regulates the gene expression in a temporally and highly coordinated manner. Preliminary studies have already shown that an increased father age influences the pattern of methylation in the sperm and umbilical cord blood of children. Moreover, intracytoplasmic sperm injection (ICSI) also leaves epigenetic signatures in umbilical cord blood. Unlike sperm, little is known about the methylation of human oocytes and their susceptibility to environmental factors. The main reason for this is the difficulty of collecting human oocytes in sufficient numbers for genome-wide analysis. The aim of this study is to analyze the methylation pattern of immature oocytes, which are not suitable for further ICSI treatment, of women with decreased fertility. The products of gene expression and also the methylation of the DNA itself can be investigated using newly developed DNA sequencing methods. Based on the results of a large number of oocytes from different women, risk assessments could be made for individual factors such as the age of the patient, as well as correlations between the occurrence of changes in gene expression and the unfulfilled desire to have children. In addition, the methylation patterns in sperms from 20 patients are to be examined as reference.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Female Patients ICSI treatment because of male subfertility |
Outcome Measures
Primary Outcome Measures
- Methylation pattern [1 day (Directly after oocyte pick-up)]
Analysis of methylation pattern in immature oocytes (not suitable for further ICSI treatment). Methylation will be pointed out as number of methylated gene loci in comparison to the overall amount of analyzed gene loci.
- Gene expression [1 day (Directly after oocyte pick-up)]
Analysis of gene expression in immature oocytes (not suitable for further ICSI treatment) will be done by quantification of selected gene transcripts (in picogram).
Eligibility Criteria
Criteria
Inclusion Criteria:
- healthy females without sterility factors
Exclusion Criteria:
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Endometriosis
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Polycystic ovary syndrome (PCO)
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Neoplasia (ovary, Uterus, breast)
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Anti-Müllerian hormone (AMH) <1 ng/ml
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Infertility treatment center Dortmund | Dortmund | NRW | Germany | 44135 |
Sponsors and Collaborators
- Infertility Treatment Center Dortmund
- University of Wuerzburg
Investigators
- Principal Investigator: Stefan Dieterle, MD, Infertility Treatment Center Dortmund
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Methylation in Germ cells